Dual optical elastography detects TGF - ß -induced alterations in the biomechanical properties of skin scaffolds.

ABSTRACT

Significance: The skin's mechanical properties are tightly regulated. Various pathologies can affect skin stiffness, and understanding these changes is a focus in tissue engineering. Ex vivo skin scaffolds are a robust platform for evaluating the effects of various genetic and molecular interactions on the skin. Transforming growth factor-beta ( TGF - ß ) is a critical signaling molecule in the skin that can regulate the amount of collagen and elastin in the skin and, consequently, its mechanical properties. Aim: This study investigates the biomechanical properties of bio-engineered skin scaffolds, focusing on the influence of TGF - ß , a signaling molecule with diverse cellular functions. Approach: The TGF - ß receptor I inhibitor, galunisertib, was employed to assess the mechanical changes resulting from dysregulation of TGF - ß . Skin scaffold samples, grouped into three categories (control, TGF - ß -treated, and TGF - ß + galunisertib-treated), were prepared in two distinct culture media-one with aprotinin (AP) and another without. Two optical elastography techniques, namely wave-based optical coherence elastography (OCE) and Brillouin microscopy, were utilized to quantify the biomechanical properties of the tissues. Results: Results showed significantly higher wave speed (with AP, p < 0.001 ; without AP, p < 0.001 ) and Brillouin frequency shift (with AP, p < 0.001 ; without AP, p = 0.01 ) in TGF - ß -treated group compared with the control group. The difference in wave speed between the control and TGF - ß + galunisertib with ( p = 0.10 ) and without AP ( p = 0.36 ) was not significant. Moreover, the TGF - ß + galunisertib-treated group exhibited lower wave speed without and with AP and reduced Brillouin frequency shift than the TGF - ß -treated group without AP, further strengthening the potential role of TGF - ß in regulating the mechanical properties of the samples. Conclusions: These findings offer valuable insights into TGF - ß -induced biomechanical alterations in bio-engineered skin scaffolds, highlighting the potential of OCE and Brillouin microscopy in the development of targeted therapies in conditions involving abnormal tissue remodeling and fibrosis.